This application for an R21 grant is designed to solidify an interdisciplinary team of basic and clinical researchers in the Center for Environmental Health Sciences at Mississippi State University for research into the environmental factors contributing to the higher mortality of cardiovascular disease (CVD) in the Deep South and among African Americans, and to position this team for participation in larger-scale on- going multi-institutional epidemiological studies. This health disparity in CVD is logically related to risk factors more prevalent in the South (which has a higher proportion of African Americans than other regions in the country.) The South is rural and highly agricultural, so the Southern populations would be expected to be routinely exposed to higher levels of pesticides than populations in many other regions. We hypothesize the following: The effects of pesticide exposure contribute to the development of CVD and are more pronounced in the African American population. Two enzymes that we have studied for many years because of their involvement in the detoxication of many pesticides are paraoxonase (PON1) and carboxylesterase (CaE). The former is known to be associated with HDL particles and the latter has recently been identified as a cholesteryl ester hydrolase that is involved in reverse cholesterol transport; therefore, both of these enzymes are involved in vascular health, and are potential biomarkers of susceptibility to CVD. We have experience biomonitoring urinary pesticide metabolites as an index of current pesticide exposure. We have developed a novel geospatial analysis of pesticide harvested crop records that predicts pesticide exposure to individuals for the previous 35 years of their lives. We have experience in cardiology and access to patients in a cardiology practice. We propose a pilot study to investigate the above listed parameters (i.e., PON1 and CaE in the blood and pesticide metabolites in the urine) of subjects recruited from the cardiology practice, and to calculate strength of associations among these factors, the degree of cardiovascular disease and the pesticide exposure estimated in the geospatial analysis model. This pilot study will be conducted following a year of planning, solidifying the interdisciplinary team, optimizing assays, and developing interactions with the project's consultants. The pilot study will position us to participate in a far more extensive study through interactions with our consultants at the University of Alabama at Birmingham. In addition, we anticipate that we will develop more simplified assay methods for PON1 and CaE that will be more amenable for use as a clinical biomarker. ? ? ? ?
|Mangum, Lee C; Mangum, Lauren H; Chambers, Janice E et al. (2016) The association of serum trans-nonachlor levels with atherosclerosis. J Toxicol Environ Health A 79:210-20|
|Coombes, R Hunter; Meek, Edward C; Dail, Mary Beth et al. (2014) Human paraoxonase 1 hydrolysis of nanomolar chlorpyrifos-oxon concentrations is unaffected by phenotype or Q192R genotype. Toxicol Lett 230:57-61|
|McDaniel, Chiquita Y; Dail, Mary Beth; Wills, Robert W et al. (2014) Paraoxonase 1 polymorphisms within a Mississippi USA population as possible biomarkers of enzyme activities associated with disease susceptibility. Biochem Genet 52:509-23|
|Coombes, R Hunter; Crow, J Allen; Dail, MaryBeth et al. (2011) Relationship of human paraoxonase-1 serum activity and genotype with atherosclerosis in individuals from the Deep South. Pharmacogenet Genomics 21:867-875|
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